The Current State of Nuclear Nephrology in Modern Medicine.

Glomerular filtration rate (GFR) is the most reliable parameter of renal function. Regarding the complexity of the gold standard inulin clearance, different estimating equations have been developed with CKD-EPI creatinine equation recommended as the most reliable one. In some clinical situations where creatinine based equations might not be valid, alternative methods are needed. Nuclear medicine methods for measuring GFR with 51Cr EDTA and 99mTc DTPA have been widely used for decades. There are different methodologies for the measurement of kidney function with radiopharmaceuticals: urinary clearance, plasma clearance, multiple plasma sampling, slope intercept, single sample plasma equation, slope only, and the gamma camera-based method. Greater precision of measuring GFR is needed in certain clinical situations. The most common are diagnosis and follow up of chronic kidney disease and definition of the beginning of replacement therapy. The assessment of renal function is also important for potential kidney donors. In recent years, with the introduction of new chemotherapeutic drugs and targeted therapy, oncologic patients treated with nephrotoxic drugs have become more commonly referred for measuring GFR. The monitoring of renal function is important during treatment in order to detect the transformation from reversible acute kidney injury to irreversible chronic kidney disease as well as in the cases of renal insufficiency reduce the dosage and prevent accumulation of the drug and avoid dosage related toxic effects. Assessment of kidney function using measured mGFR will be an important milestone in the creation of more accurate and expanding personalized medicine principle in current onconephrology practice.

Comparative analysis of different nuclear medicine techniques in evaluation of renal function.

INTRODUCTION: Nuclear medicine (NM) methods play an important role in the evaluation of renal function in a wide range of clinical indications. The aim of our study was to evaluate the correlation between measured GFR (mGFR) obtained by the three-plasma sample slope-intercept NM method (TPSM) - reference method vs. estimated GFR (eGFR) using Fleming's single plasma sample method (SPSM) at 120 min, 180 min, and 240 min and correlation of reference method with eGFR with camera-based Gates' protocol. MATERIAL AND METHODS: A total of 82 subjects (33 male/49 female) with a mean age of 54.87 ± 15.65 years were included and mGFR value was obtained by the three-plasma sample slope-intercept NM method and eGFR was obtained with Fleming's single sample method. eGFR was also quantified with the camera-based Gates' protocol after i.v. application of [99mTc]Tc-DTPA. RESULTS: Our study revealed a very strong positive significant correlation between all three SPSMs with the TPSM as the reference method. Between the Gates' method and the TPSM in the group of patients with mGFR ≥ 61-84 mL/min/1.73 m2 and mGFR ≥ 84 mL/min/1.73 m2, a moderate positive statistically significant correlation was obtained. CONCLUSIONS: The SPSM method shows a very strong correlation with the reference and low bias in all three groups of patients and can be routinely used for GFR estimation.

The Evaluation of Sentinel Lymph Node Biopsy Using Radiocolloid in First Stage Endometrial Cancer.

Objectives: Detection of a sentinel lymph node (SLN) in patients with endometrial cancer (EC) reduces the rate of unnecessary systemic lymph dissection. The aim of this study was to assess the SLN detection rate, accuracy of the method using Tc-99m-SENTI-SCINT and the rate of metastatic nodal involvement in patients with preoperative first stage EC. Methods: A prospective study of SLN biopsy of 41 patients with stage I EC was conducted after cervical application of 4mCi Tc-99m-SENTI-SCINT. Planar lymphoscintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT) of the pelvis were performed, followed by site-specific lymphadenectomy in intermediate-risk patients if no SLN was detected per hemipelvis and pelvic lymphadenectomy in all high-risk patients. Results: Pre-operative detection rate of planar lymphoscintigraphy was 80.49 [95% confidence interval (CI): 68.36-92.62] and of SPECT/CT 95.12 (95% CI: 88.52-101.7). The total intraoperative SLN detection rate was 95.12 (95% CI: 88.52-101.7) per patient and 26.83 (95% CI: 19.91-33.75) bilaterally. The average number of SLNs removed was 1.6±0.8. The most common anatomical location of SLN was the right external iliac region. The SLN metastatic rate was 17%. Both sensitivity and negative predictive value regarding metastatic involvement were 100%. Conclusion: The SLN detection rate, sensitivity and negative predictive value using Tc-99m-SENTI-SCINT in patients with EC in our study were high. The application of ultra-staging in the histopathological analysis of SLN increases the detection of nodal metastases and improves the staging in these patients.

Molecular imaging of HER2 receptor: Targeting HER2 for imaging and therapy in nuclear medicine.

Targeting HER 2 for imaging and therapy in nuclear medicine has been used with a special emphasis on developing more powerful radiopharmaceuticals. Zirconium-89 plays an essential role in immune PET imaging so was used labeled with anti-HER2 antibody (Trastuzumab and Pertuzumab). Also there were attempts with other PET tracers as Cuprum-64 and Galium-68, as well as SPECT radiopharmaceuticals Indium-111 and Technetium- 99m. Regarding antibody pharmacokinetic that is not quite appropriate for imaging acquisition, several smaller molecules with shorter residence times have been developed. These molecules called nanobody, affibody, minibody do not compromize HER2 receptor affinity and specificity. Excess of Trastuzumab do not block the affinity of labeled affibodies. Silica nanoparticles have been conjugated to anti-HER2 antibodies to enable targeting of HER2 expressing cells with potential of drug delivery carry for antitumor agents and b(beta) or a(alfa) emitting radioisotopes commonly used for radionuclide therapy, as Iodine-131, Lutetium-177, Yttrium-90, Rhenium-188 and Thorium-277.

Decoupling channel count from field of view and spatial resolution in single-sensor imaging systems for fluorescence image-guided surgery.

Significance: Near-infrared fluorescence image-guided surgery is often thought of as a spectral imaging problem where the channel count is the critical parameter, but it should also be thought of as a multiscale imaging problem where the field of view and spatial resolution are similarly important. Aim: Conventional imaging systems based on division-of-focal-plane architectures suffer from a strict relationship between the channel count on one hand and the field of view and spatial resolution on the other, but bioinspired imaging systems that combine stacked photodiode image sensors and long-pass/short-pass filter arrays offer a weaker tradeoff. Approach: In this paper, we explore how the relevant changes to the image sensor and associated image processing routines affect image fidelity during image-guided surgeries for tumor removal in an animal model of breast cancer and nodal mapping in women with breast cancer. Results: We demonstrate that a transition from a conventional imaging system to a bioinspired one, along with optimization of the image processing routines, yields improvements in multiple measures of spectral and textural rendition relevant to surgical decision-making. Conclusions: These results call for a critical examination of the devices and algorithms that underpin image-guided surgery to ensure that surgeons receive high-quality guidance and patients receive high-quality outcomes as these technologies enter clinical practice.

Ultrasound features and preoperative accuracy of the fine needle aspiration biopsy in detection of thyroid carcinomas.

OBJECTIVE: To analyze the ultrasound (US) characteristics and fine needle biopsy (FNAB) of thyroid carcinomas (TCs) prior to surgery and compare with postoperative histopathology and to determine FNAB sensitivity and specificity. MATERIAL AND METHODS: Retrospective analysis of the US data during 1999-2015 was performed, as well as analysis of FNAB results and using histopathology report as "gold standard" the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of this method was evaluated. RESULTS: Data revealed that tumors >51 mm were declining by 50% in the period 2011-2015 compared to 2005-2010 or by 18% 2011-2015 compared to 1999-2004 and significant increase was detected in diagnosis of multicentric tumors. The analysis revealed that FNAB has sensitivity = 65.7% CI (0.59% - 0.71%) and specificity = 50% CI (0.43%-0.56%), PPV = 56.9% and NPV = 59.2%. CONCLUSION: We found increasing detection of smaller TCs, as well as more frequent detection of multicentricity of the neoplastic foci. FNAB results in our study revealed low sensitivity and specificity. Major limitation of the study was inability to exactly separate US guided from non US guided FNAB in evaluation of the sensitivity and specificity, due to retrospective nature of the analysis. Further studies evaluating only US guided FNAB should be performed.

Universal salt iodization potentially contributes to health equity: socio-economic status of children does not affect iodine status.

OBJECTIVES: Many studies have shown that socio-economic status (SES) contributes to health inequalities, with nutrition as one of the major risk factors. Iodine intake entirely depends on external sources, and deficiencies are known to be more prevalent in lower social groups, especially in countries with limited access to iodized salt. This study aimed to determine the influence of SES on iodine status and iodine availability from household salt in North Macedonia. METHODS: Using cluster sampling, 1,200 children were recruited, and 1,191 children participated (response rate: 99.2%). Iodine status was assessed through urinary iodine concentration (UIC), and iodine availability through iodine content in household salt requested from participants. SES was assessed using standardized Family Affluence Score (FAS). RESULTS: No statistically significant correlation was found between FAS and iodine in salt. Median regression revealed no significant associations of middle vs. low FAS (ß=0.00; 95%-confidence interval (CI)=[-0.61, 0.62]; p=0.999) or high vs. low affluence (ß=0.48; 95% CI=[-1.37, 0.41]; p=0.291) with iodine content in household salt. UIC levels were significantly lower in middle FAS children compared to low FAS children (ß=-16.4; 95% CI=[-32.3, -0.5]; p=0.043). No statistically significant differences in UIC were found between children with high and low affluence (ß=-12.5; 95% CI=[-35.5, 10.5]; p=0.287), possibly due to lowered statistical power for this comparison. CONCLUSIONS: Universal salt iodization (USI) proves to be a cost-effective measure for appropriate iodine intake in healthy children and adults, irrespective of their social status. It can thus be concluded that USI contributes to reducing health inequalities related to iodine status among population of different social strata.

Preoperative detection of sentinel lymph node in patients with endometrial cancer - comparison of planar lymphoscintigraphy, spect and SPECT/CT.

BACKGROUND: Sentinel lymph node (SLN) mapping allows minimal invasive assessment of lymph node status in patients with early-stage endometrial cancer (EC). Intraoperative detection of SLNs is based on the results obtained from preoperative nuclear medical images. The purpose of this study was to compare the data obtained from planar lymphoscintigraphy (PL), single-photon emission computed tomography (SPECT), and SPECT with computed tomography (SPECT/CT) for preoperative SLN detection in patients with EC. MATERIAL AND METHODS: A total of 44 images in 22 patients with early-stage EC (22 PL, 9 SPECT and 13 SPECT/CT) were analyzed. The scans were performed in the period 2018-2020 at the Institute of Pathophysiology and Nuclear Medicine in Skopje. Thirteen patients underwent PL and SPECT/CT and nine patients underwent PL and SPECT after cervical injection of 4 mCi 99mTc-SENTI-SCINT on the day of surgery. Descriptive statistics, Wilcoxon Matched Pairs Test, and Spearman rank R coefficient were used for data analyses. RESULTS: Twenty-two patients with mean age of 61.1 ± 7.5 and body mass index (BMI) 34.62 ± 6.4 kg/m2 were included in the study. In four patients (18.2%) SLN was not detected on PL. Detection rate on SPECT and SPECT/CT was 100%. The average number of detected SLN was 1.4 ± 1.05, 2.2 ± 1.1 и 2.15 ± 1.1 on PL, SPECT and SPECT/CT respectively. We found a statistically significant difference in the number of detected SLNs on PL vs SPECT/CT (p = 0.0077). The most common SLN location on SPECT/CT was the right internal iliac followed by the left common iliac region. CONCLUSIONS: The results of the presented study indicate a higher diagnostic value of SPECT/CT in terms of SLN detection and exact anatomic localization as compared to planar lymphoscintigraphy (PL).

Hexachromatic bioinspired camera for image-guided cancer surgery.

Cancer affects one in three people worldwide. Surgery remains the primary curative option for localized cancers, but good prognoses require complete removal of primary tumors and timely recognition of metastases. To expand surgical capabilities and enhance patient outcomes, we developed a six-channel color/near-infrared image sensor inspired by the mantis shrimp visual system that enabled near-infrared fluorescence image guidance during surgery. The mantis shrimp's unique eye, which maximizes the number of photons contributing to and the amount of information contained in each glimpse of its surroundings, is recapitulated in our single-chip imaging system that integrates arrays of vertically stacked silicon photodetectors and pixelated spectral filters. To provide information about tumor location unavailable from a single instrument, we tuned three color channels to permit an intuitive perspective of the surgical procedure and three near-infrared channels to permit multifunctional imaging of optical probes highlighting cancerous tissue. In nude athymic mice bearing human prostate tumors, our image sensor enabled simultaneous detection of two tumor-targeted fluorophores, distinguishing diseased from healthy tissue in an estimated 92% of cases. It also permitted extraction of near-infrared structured illumination enabling the mapping of the three-dimensional topography of tumors and surgical sites to within 1.2-mm error. In the operating room, during surgical resection in 18 patients with breast cancer, our image sensor further enabled sentinel lymph node mapping using clinically approved near-infrared fluorophores. The flexibility and performance afforded by this simple and compact architecture highlights the benefits of biologically inspired sensors in image-guided surgery.

Platlet-Rich Plasma - Review of Literature.

Wound healing is a dynamic and physiological process for restoring the normal architecture and functionality of damaged tissue. Platelet-rich plasma (PRP) is an autologous whole blood product that contains a large number of platelets in a small volume of plasma with complete set of coagulation factors, which are in physiological concentrations. PRP has haemostatic, adhesive properties and acts supraphysiologically in the process of wound healing and osteogenesis. Platelets play a very important role in the wound healing process by providing growth factors that enhance the rate and quality of wound healing by many different mechanisms. The aim of this review is to describe: the biology of platelets and their role in the wound healing process, the terminology of platelet rich products, PRP preparation, activation and concentration of PRP, as well as the use of PRP in plastic surgery.

Prognostic factors in thyroid carcinomas: a 17-year outcome study

ABSTRACT Objectives The aim of our study was to evaluate the survival rate of all thyroid carcinomas (TCs) diagnosed in the 1999-2015 period in the Republic of North Macedonia and to analyze the prognostic influence of several characteristics on development of distant metastases, as well as to analyze the prognostic effect of seven clinical and constitutional features on mortality. Material and methods A retrospective analysis of medical data from all TCs diagnosed in 1999-2015 was performed. The survival rate of all types of TCs was estimated using the Kaplan Meier method. Univariate and multivariate logistic regression analysis was applied for evaluation of the predictive role of seven clinical and constitutional characteristics for development of distant metastases, and the univariate Cox-proportional model was applied for evaluation of the predictors for mortality. Results A total of 422 TC cases were diagnosed in the 17-year period, with an average survival time of 212.99 months. Results of the univariate regression analysis showed that dimension at initial ultrasound and histopathological type of tumor were significantly predictive variables for distant metastases. Multifocal tumors vs. unifocal tumors < 15 mm significantly increased the probability of distant metastases by 7.401 (p = 0.005, 95% CI = 1.817-30.190) times. Age, initial lymph node involvement, number of radioiodine therapies, and histopathology of the tumor were selected as independent significant predictors for mortality. Conclusion Our results showed an excellent overall prognosis of thyroid tumors in the Macedonian population. The dimension of the tumor, multifocality, and histopathological type were the most relevant prognostic predictive features for development of distant metastases.

Prognostic factors in thyroid carcinomas: a 17-year outcome study.

Objectives The aim of our study was to evaluate the survival rate of all thyroid carcinomas (TCs) diagnosed in the 1999-2015 period in the Republic of North Macedonia and to analyze the prognostic influence of several characteristics on development of distant metastases, as well as to analyze the prognostic effect of seven clinical and constitutional features on mortality. Material and methods A retrospective analysis of medical data from all TCs diagnosed in 1999-2015 was performed. The survival rate of all types of TCs was estimated using the Kaplan Meier method. Univariate and multivariate logistic regression analysis was applied for evaluation of the predictive role of seven clinical and constitutional characteristics for development of distant metastases, and the univariate Cox-proportional model was applied for evaluation of the predictors for mortality. Results A total of 422 TC cases were diagnosed in the 17-year period, with an average survival time of 212.99 months. Results of the univariate regression analysis showed that dimension at initial ultrasound and histopathological type of tumor were significantly predictive variables for distant metastases. Multifocal tumors vs. unifocal tumors < 15 mm significantly increased the probability of distant metastases by 7.401 (p = 0.005, 95% CI = 1.817-30.190) times. Age, initial lymph node involvement, number of radioiodine therapies, and histopathology of the tumor were selected as independent significant predictors for mortality. Conclusion Our results showed an excellent overall prognosis of thyroid tumors in the Macedonian population. The dimension of the tumor, multifocality, and histopathological type were the most relevant prognostic predictive features for development of distant metastases.

AROME-ESO Oncology Consensus Conference: access to cancer care innovations in countries with limited resources. Association of Radiotherapy and Oncology of the Mediterranean Area (AROME-Paris) and European School of Oncology (ESO - Milan).

PURPOSE: Cancer is a leading cause of mortality worldwide. Its incidence is still increasing, particularly in developing countries. Recent progresses further strengthen the differences between low/middle and high-income countries. This situation calls for joint action to reduce inequities in cancer outcomes among the patients. The Association of Radiotherapy and Oncology of the Mediterranean Area (AROME) and the European School of Oncology (ESO), have initiated joint conferences devoted to access to innovations in oncology in the Mediterranean area. The heterogeneity of the economic, political and cultural situations of the different participating countries, offers the opportunity to develop consensus conference. METHODS: Cancer prevention and treatment strategies were discussed according to existing international guidelines. The Scientific committee prepared 111 questions with an objective to prioritize the access to treatments and innovations in low/middle-income Mediterranean countries. The results from the votes of 65 oncology experts, coming from 16 countries and 33 institutions have been analysed and access priorities classified accordingly. RESULTS: Ninety six percent of the proposed general recommendations concerning national health care strategies, oncology education, and treatment organization were considered to be high priorities. Regarding access to systemic treatments, 41% of the drugs without validated predictive markers and 53% of those with validated predictive markers were considered to be 1st level priority. Only 4 biological tests were considered to be 1st level priority to access to innovation. CONCLUSIONS: AROME-ESO consensus offers to cancer specialists from developing countries a basis for discussion with health authorities and payers on the prioritization of access to innovations in cancer care.

Molecular Imaging in Breast Cancer.

Breast cancer (BC) is the most common cancer among females with more than 2 million new cases diagnosed worldwide in 2018. Although the prognosis in the majority of cases in the early stages combined with appropriate treatment is positive, there are still about 30% of patients who will develop locoregional diseases and distant metastases. Molecular imaging is very important in the diagnosis, staging, follow-up, and radiotherapy planning. Additionally, it is useful in characterizing lesions, prognosis, and therapy response in BC patients. Nuclear medicine imaging modalities (SPECT and PET) are of indispensable importance in diagnosis (positron emission mammography), staging (sentinel lymph node detection), and follow-up with18F-FDG and tumor characterization. Among many available PET tracers, the most commonly used are 18F-FLT, 18F-FES, 18F-FDHT, 64Cu DOTA trastuzumab (bevacizumab), 68Ga-PSMA, 68Ga-RM2 (gastrin-releasing peptide receptor), 18F-fluorooctreotide (SSTR), and 68Ga-TRAP (RGD)-3αvß3-integrin. Molecular imaging helps in evaluation of tumor heterogeneity, allowing a shift from one-size-fits-all-approach to era of personalized medicine and precision oncology.

Thyroid cancer detection rate and associated risk factors in patients with thyroid nodules classified as Bethesda category III.

Background Ultrasound guided fine-needle aspiration (FNA) is a standard procedure for thyroid nodules management and selecting patients for surgical treatment. Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS), as stated by The Bethesda System for Reporting Thyroid Cytopathology, is a diagnostic category with an implied malignancy risk of 5-15%. The aim of our study was to review cytology and histopathology reports, as well as clinical and ultrasound data, for thyroid nodules reported as AUS/FLUS, in order to evaluate the malignancy rate and to assess factors associated with malignant outcome. Patients and methods A total of 112 AUS/FLUS thyroid nodules in 105 patients were evaluated, of which 85 (75.9%) were referred to surgery, 21 (18.8%) were followed-up by repeat FNA and 6 nodules (5.3%) were clinically observed. Each was categorized in two final diagnostic groups - benign or malignant, which were further compared to clinical data of patients and ultrasonographic features of the nodules. Results Final diagnosis of malignancy was reached in 35 cases (31.2%) and 77 (68.8%) had benign lesions. The most frequent type of cancer was papillary thyroid carcinoma (PTC) - 58.1% PTC and 25.8% had follicular variant of PTC. Patients' younger age, smaller nodule size, hypoechoic nodule and presence of calcifications were shown to be statistically significant risk factors for malignancy. Conclusions The rate of malignancy for the AUS/FLUS diagnostic category in our study was higher than estimated by the Bethesda System. Clinical and ultrasound factors should be considered when decision for patient treatment is being made.

Absent 99mTc-MIBI Uptake in the Thyroid Gland during Early Phase of Parathyroid Scintigraphy in Patients with Primary and Secondary Hyperparathyroidism.

BACKGROUND: Thyroid uptake of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) during parathyroid scintigraphy can be affected by various conditions. AIM: To evaluate the frequency of absent 99mTc-MIBI uptake by the thyroid gland in the early phase of dual-phase parathyroid scintigraphy. METHODS: The early planar images of dual phase Tc99m MIBI parathyroid scintigraphy from 217 patients performed between 2014 and 2017 were retrospectively analysed. Patients were divided into two groups. The first group included 147 patients with primary hyperparathyroidism and the second group included 70 patients with chronic renal failure. Patient records, laboratory and ultrasonographic data were analysed in all patients. Descriptive statistic was used for data analysis. RESULTS: Out of all patients in the first group, 18 patients (12.24%) showed absent thyroid uptake. Thyroidectomy was performed in 44.4% of these patients, and the rest of them had some thyroid disease. Only one patient had no thyroid or another chronic disease. In the second group, 8 patients (11.42%) presented with absent thyroid uptake of MIBI. Among them, 5 patients had no history of thyroid disease and had been on hemodialysis programme, and 3 patients had hypothyroidism. CONCLUSION: Absent 99mTc-MIBI uptake in the thyroid during the early phase of parathyroid scintigraphy is most frequently related to thyroid disease. A small proportion of patients with chronic renal failure can present with absent 99mTc-MIBI uptake in the thyroid as well. The mechanism for this alteration is still unclear and needs further investigation.

Sentinel Lymph Node Detection in Colorectal Cancer - First Experience.

BACKGROUND: Colorectal cancer (CRC) is the second commonest cancer in women, the third in men, being the fourth commonest cause of cancer death. The most important factor for prognosis and staging in CRC patients is the status of the regional lymph nodes (LN). AIM: To implement the method for sentinel lymph node (SLN) detection in CRC patients using radiocolloid, and test its detection rate, sensitivity, accuracy, negative predictive value and the possibility for upstaging. MATERIAL AND METHODS: The study included 40 CRC patients, age 63 ± 14 years, without LNs detected on CT or MRI. SLN detection was performed after endoscopically peri- and intratumoral injection of 99mTc-SENTISCINT. All patients underwent resection with systemic lymphadenectomy, and the SLNs were detected ex vivo. Pathohistology was performed to all resected LNs. RESULTS: The identification rate was 95%, the accuracy of the procedure was 92.1%, the negative predictive value was 86.95%, the sensitivity was 83.3%, and the upstage was 22.5%. CONCLUSION: Identification of SLNs in CRC patients with this method is possible and the detection rate, negative predictive value, accuracy and sensitivity are reliable. We expect to contribute in the upstaging of stage II CRC patients and the selection of appropriate oncology treatment protocols.

Normal Values of Tissue-Muscle Perfusion Indexes of Lower Limbs Obtained with a Scintigraphic Method.

Introduction Muscle perfusion is a physiologic process that can undergo quantitative assessment and thus define the range of normal values of perfusion indexes and perfusion reserve. The investigation of the microcirculation has a crucial role in determining the muscle perfusion. Materials and method The study included 30 examinees, 24-74 years of age, without a history of confirmed peripheral artery disease and all had normal findings on Doppler ultrasonography and pedo-brachial index of lower extremity (PBI). 99mTc-MIBI tissue muscle perfusion scintigraphy of lower limbs evaluates tissue perfusion in resting condition "rest study" and after workload "stress study", through quantitative parameters: Inter-extremity index (for both studies), left thigh/right thigh (LT/RT) left calf/right calf (LC/RC) and perfusion reserve (PR) for both thighs and calves. Results In our investigated group we assessed the normal values of quantitative parameters of perfusion indexes. Indexes ranged for LT/RT in rest study 0.91-1.05, in stress study 0.92-1.04. LC/RC in rest 0.93-1.07 and in stress study 0.93-1.09. The examinees older than 50 years had insignificantly lower perfusion reserve of these parameters compared with those younger than 50, LC (p=0.98), and RC (p=0.6). Conclusion This non-invasive scintigraphic method allows in individuals without peripheral artery disease to determine the range of normal values of muscle perfusion at rest and stress condition and to clinically implement them in evaluation of patients with peripheral artery disease for differentiating patients with normal from those with impaired lower limbs circulation.

Synergistic Effect of Hyperoxia and Biotrauma On Ventilator-Induced Lung Injury.

Patients undergoing mechanical ventilation in intensive care units (ICUs) may develop ventilator-induced lung injury (VILI). Beside the high tidal volume (Vt) and plateau pressure (Pplat), hyperoxia is supposed to precipitate lung injury. Oxygen toxicity is presumed to occur at levels of fraction of inspired oxygen (FiO2) exceeding 0.40. The exposure time to hyperoxia is certainly very important and patients who spend extended time on mechanical ventilation (MV) are probably more exposed to severe hyperoxic acute lung injury (HALI). Together, hyperoxia and biotrauma (release of cytokines) have a synergistic effect and can induce VILI. In the clinical practice, the reduction of FiO2 to safe levels through the appropriate use of the positive end expiratory pressure (PEEP) and the alignment of mean airway pressure is an appropriate goal. The strategy for lung protective ventilation must include setting up FiO2 to a safe level that is accomplished by using PaO2/FiO2 ratio with a lower limit of FiO2 to achieve acceptable levels of PaO2, which will be safe for the patient without local (lungs) or systemic inflammatory response. The protocol from the ARDS-net study is used for ventilator setup and adjustment. Cytokines (IL-1, IL-6, TNFα and MIP-2) that are involved in the inflammatory response are determined in order to help the therapeutic approach in counteracting HALI. Computed tomography findings reflect the pathological phases of the diffuse alveolar damage. At least preferably the lowest level of FiO2 should be used in order to provide full lung protection against the damage induced by MV.